Future is in heart transplantation

1. The Future is
Heart Transplantation
Jon A. Kobashigawa, M.D.
DSL/Thomas D. Gordon Professor of Medicine
Associate Director, Cedars-Sinai Heart Institute
Director, Advanced Heart Disease Section
Director, Heart Transplant Program
Cedars-Sinai Medical Center, Los Angeles, California
Cedars-Sinai Heart Institute

2. Heart Transplant or MCS?
• Heart Transplantation is a well established treatment for
end-stage heart disease (ESHD).
• With improvements in immuno-suppression, peri-
operative care and post-transplant management,
rejection rates have sharply declined and survival rates
have improved.
• It is currently THE ONLY LONG-TERM solution for the
management of ESHD.
• Patients have the potential to resume a normal lifestyle.

3. Era 1 vs. Era 2: p = 0.94
Era 1 vs. Era 3: p = 0.02
Post-Transplant Survival for adult recipients:
All statuses combined
•Era 3 had significantly higher survival within 2 years compared to Era 1, in
spite of increased % Status 1A transplants
Era 1: 7/12/04-5/11/06 (N=3272) Era 2: 7/12/06-7/11/08 (N=3707)
Era 3: 7/12/07-5/11/10 (N=3364)

4. % of Patients with 1st-Year Rejection
Cedars-Sinai Heart Institute
Pravastatin
MMF
Tacrolimus

5. Heart Transplant or MCS?
• MCS is an evolving technology.
• Durability remains limited.
• There is no long-term solution for RV support.
• The totally implantable TAH remains elusive – patients
are lumbered with paraphernalia.
• Morbidity, complications and costs remain substantial.
• Have you ever seen a patient with MCS go for a swim?

6. ADULT HEART RECIPIENTS
Cross-Sectional Analysis
Functional Status of Surviving Recipients
(Follow-ups: January 2000 – June 2011)
ISHLT 2012
J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095

7. Chimerism and Tolerance
• Induction of tolerance, which obviates the need for maintenance
immunosuppression, is the holy grail in organ transplantation.
• Currently, ongoing immunosuppressive therapy is deemed
essential to ensure long-term graft survival however, these drugs
have many serious adverse effects.
• The development of chimerism (existence of 2 allogeneic cell
lines) in animal studies has been demonstrated to prevent rejection
and the opportunity to discontinue immunosuppression entirely. 1
1 Ilstad ST et al. Curr. Opin. Organ Transplant. 2011; 16: 343-344
Cedars-Sinai Heart Institute

8. Chimerism and Immune Tolerance:
Kidney Transplant Study
• Leventhal et al. investigated combined renal and stem cell
transplants with nonmyeloablative conditioning in 8 human patients:
- All eight patients received human leukocyte antigen mismatch
kidneys and graft facilitating cells and hematopoietic stem cells.
- Patients received nonmyeloablative conditioning with
fludarabine, 200-centrigray total body irradiation, and
cyclophosphamide in addition to post-transplant
immunosuppression with tacrolimus and mycophenolate.
Leventhal J. et al. Sci Transl Med 2012; 4(124) 124ra28
Cedars-Sinai Heart Institute

9. Algorithm for nonmyeloablative conditioning, kidney and
hematopoietic stem cell transplant, and postop immunosuppression
Leventhal J. et al. Sci Transl Med 2012; 4(124) 124ra28
FCRx: tolerance promoting facilitating cell based hematopoietic stem cell graft
Cy: cyclophoshomide

10. Chimerism and Immune Tolerance: Results
 5 patients experienced durable chimerism and were
subsequently weaned off immunosuppression.
 2 patients did not have durable chimerism but were sustained
on low-dose monotherapy with tacrolimus.
 1 patient acquired a viral sepsis at 2 months post-transplant and
experienced renal artery thrombosis with need for redo-kidney
transplant.
 Studies in heart transplant patients are currently underway.
Leventhal J. et al. Sci Transl Med 2012; 4(124) 124ra28
Cedars-Sinai Heart Institute

11. Heart on the Organ Care System:
Expanding the Donor Pool?
Beating donor heart
in the protected box

12. Cedars-Sinai Heart Institute

13. By using a process called
whole organ
decellularization,
scientists from the
University of Minnesota
Center for
Cardiovascular Repair
grew functioning heart
tissue by taking dead rat
and pig hearts and
reseeding them with a
mixture of live cells.
Whole organ engineering
Dr Doris Taylor

14. Cedars-Sinai Heart Institute

15. Who is the longest living
heart transplant recipient?
A B
C D
Joseph Quilty Gordon Gadow
Baby Faye Rod Blagojevich

16. B: Gordon Gadow

17. This picture series is currently not
possible with MCS
Patient GG,
age 71
Patient GG,
age 40

18. Adult Heart
Transplants-
Survival,
2006-2012,
ISHLT
registry
(JHLT. 2014; 33(10):
996-1008)
50%
75%
Four year survival:
Continuous flow
LVAD/BiVAD
implant survival,
2008-13
INTERMACS,
(JHLT. 2014;33(6):555-64)
vs

19. Who is Kelly Perkins?
A B
C D
A disabled MCS patient A 4 year MCS Survivor
A heart transplant recipient
who climbed 10 peaks
in 4 days
A heart transplant recipient
not requirng immuno-
suppressive therapy

20. C: A heart transplant recipient
who climbed 10 peaks in 4 days

21. Kelly Perkins Climbed 10 Teton Peaks in
4 Days at age 47 years
(August 2009)
She received her heart transplant in 1995

23. MCS vs Transplant: Cardiopulmonary
exercise test (CPET) comparison
• Compared cohort of LVAD
patients (n=25) and transplant
patients (n=74) at single center
• Pre and post procedure CPET
tests
• Similarly low exercise tolerance
and peak VO2 found pre-
transplant
• However, significantly lower
peak VO2 found post-
procedure in LVAD patients
compared to post-OHT patients
• LVAD does not appear to
improve peak VO2 as much as
transplant Dunlay et al. J Cardiac Fail 2014;20:548-554

24. MCS leads to less hospitalization and is cheaper
than transplant.
This is…
A B
C D
An established fact Balderdash
Hospitalization for MCS
is longer
but overall costs are lower
Costs for Transplant and
MCS are equivalent

25. B: Balderdash

26. Rehospitalization rate: MCS vs OHT
MCS OHT
1-year freedom from
rehospitalization
15-39%1-4 ~55%5
1. Goldstein et al. J Heart Lung Transplant. 2013;32(4)S98
2. Bonde et al. J Heart Lung Transplant. 2011;30(4)S9
3. Dunlay et al. Circ Cardiovasc Qual Outcomes. 2014; 7: A208
4. Hasin et al. J Am Coll Cardiol 2013; 61:153–63
5. Stehlik et al. J Heart Lung Transplant 2012; 31; 1052

27. ADULT HEART RECIPIENTS
Rehospitalization Post-transplant of Surviving Recipients
(Follow-ups: January 2000 – June 2011)
ISHLT 2012
J Heart Lung Transplant. 2012 Oct; 31(10): 1045-1095

28. What therapy gives you the best
chance of providing your loved patient
with a disabling stroke, GI bleed,
hemolysis and serious infection
All at the SAME time?
A B
C D
IV Inotropes MCS
Heart Transplant
Cardiac Resynchronization
Therapy

29. B: MCS

31. The Future should be Heart
Transplant when…..
• It beats MCS in predicted median survival
• It beats MCS in functional capacity and quality of life
• It beats MCS in morbidity of suffering
• It’s natural!

33. Thank You